The overall goal of this project is to understand what regulates the post-embryonic regeneration of the olfactory periphery. This proposal focuses on one major aspect of the project - the proliferation of new olfactory receptor neurons and associated cells in adult animals. Continuous proliferation and turnover of olfactory receptor neurons, even in adults, is a feature of humans that is also expressed in the animal model used in this study. The three specific aims are 1) What genes are associated with proliferation of new olfactory cells? 2) How do local and hormonal factors alter proliferation of olfactory cells? and 3) What functional changes are correlated with proliferation, maturation, and differentiation of olfactory cells? To investigate these issues, this proposal will use critical advantageous features of the lobster olfactory system, which include a wealth of knowledge about the functional organization of this system, continuous turnover of adult olfactory tissue that can be modulated by damage and hormones (as in mammals), and a developmental axis to its olfactory organ in which the zones of proliferation, maturation, and senescence, are physically separated (not so in mammals). Consequently, these experiments are possible in the lobster, but not in other prominent invertebrate models such as Drosophila and C. elegans which lack post-embryonic turnover of olfactory neurons. The experimental design will include molecular techniques including searches for novel genes (by representational difference analysis) and homologous genes (by RT-PCR), analysis of expression patterns of genes and their products (by in-situ hybridization and immunocytochemistry), and analysis of function (by patch-clamp and sing]e cell electrophysiology). These studies of stem cell-like activity and neurogenesis in post-embryonic adult animals are important since these regenerative processes are not only of basic importance to understanding regulation of function of a sensory organ, but also have the practical importance of helping us understand how to compensate for loss of activity and function through regulation by control systems.